JP2003095981A - Medicine composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a medicine composition having excellent sense of administration in contrast with unpleasant sense including difficulty in swallowing of the medicine composition formulated with colestimide, polycarbophil and their salts being resin preparations. SOLUTION: This medicine composition comprises one kind selected from the group consisting of colestimide, polycarbophil and their salts being resin preparations and one or more kinds selected from the group consisting of menthol, camphor, menthe oil, eucalyptus oil, peppermint oil, chlorobutanol and menthyl lactate being refringerants.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an unpleasant sensation such as a difficulty in swallowing when taking a resin formulation of colestimide, polycarbophil and salts thereof.
The present invention relates to providing a pharmaceutical composition having an excellent feeling of ingestion. Specifically, it comprises colestimide, polycarbophil and its salts, and one or more cooling agents selected from the group consisting of menthol, camphor, peppermint oil, eucalyptus oil, peppermint oil, chlorobutanol and menthyl lactate. The composition for topical application has remarkably improved feeling of ingestion.

[0002]

2. Description of the Related Art Up to now, there have been known pharmaceutical compositions in which any one of resin preparations such as colestimide, polycarbophil and salts thereof has been individually blended. However, menthol, camphor, peppermint oil, eucalyptus and eucalyptus have been known. There is no known pharmaceutical composition containing a cooling agent such as oil, peppermint oil, chlorobutanol, and menthyl lactate. Drugs are usually absorbed from the digestive tract, enter the blood, and mainly act at their respective target sites. However, in recent years, drugs such as resin preparations have been developed which show a characteristic action in the digestive tract without being digested or absorbed. These include colestimide commonly used for hyperlipidemia and polycarbophil calcium used for irritable bowel syndrome. Although different symptoms are used respectively, colestimide is an anion exchange resin that inhibits absorption of cholesterol, and polycarbophil calcium is a resin formulation called polyacrylic resin that regulates water in the intestine. However, the characteristics of resin formulations are that each drug has a large amount of one dose, and its chemical composition makes it easy to absorb water and swell, which causes discomfort when swallowing. It was difficult to say that the person had a sufficiently satisfactory dose.

Cooling agents such as menthol, camphor, peppermint oil, eucalyptus oil, peppermint oil, chlorobutanol, and menthyl lactate are widely used in general foods and quasi drugs. However, the mechanism related to nerve transmission such as feeling of taking has not yet been clarified at present.

[0004]

Due to the characteristics of the above-mentioned resin formulation, a large amount of a single dose is taken, and its chemical composition makes it easy to swell due to absorption of water, which makes it difficult to swallow when taking the drug. It was unavoidable to make sense. However, this is an obstacle to improving the compliance of drug users. Therefore, in order for patients to properly use these useful drugs, it is desired to develop a formulation which is not uncomfortable and has an excellent ingestion feeling. An object of the present invention is to provide a pharmaceutical composition with improved ingestion sensation of colestimide, polycarbophil and salts thereof, which are resin formulations having an unpleasant ingestion sensation such as dysphagia.

[0005]

Means for Solving the Problems As one of the causes of the difficulty in swallowing when taking a resin preparation, it is considered that there is a physiological stricture site in the esophagus, and the mucous membrane or the like is stimulated when passing through the site. The present inventors have studied the drug shape and the compounded drug in order to reduce such stimulation of sensory nerves. Regarding drug form, tablets with high drug content,
There are granules, which are coated with film and designed to be easy to drink. Therefore, as a candidate for a combination drug that improves the feeling of ingestion, we examined both a combination of a cooling agent and a local anesthetic such as lidocaine as a drug that paralyzes the sensory nerves of the mucous membrane and inhibits the transmission of stimulation. However, the local anesthetics such as lidocaine newly cause discomfort such as numbness in the oral cavity, and the effect of improving the feeling of ingestion over the cooling agent was not obtained.

Based on the above findings, a refreshing agent such as menthol, camphor, peppermint oil, eucalyptus oil, peppermint oil, chlorobutanol, and menthyl lactate is uncomfortable when the resin preparations cholestimide, polycarbophil, and salts thereof are taken. Impairs or significantly reduces sensory transmission,
The present invention has been completed by finding that the feeling of taking a drug is remarkably improved. That is, the present invention is a pharmaceutical composition comprising a resin preparation and a cooling agent. The resin formulation is one selected from the group consisting of colestimide, polycarbophil and salts thereof, and the cooling agent is selected from the group consisting of menthol, camphor, peppermint oil, eucalyptus oil, peppermint oil, chlorobutanol and menthyl lactate. It is one kind or two or more kinds selected.

The polycarbophil and its salts mean pharmaceutically acceptable salts, and specifically include calcium salt, sodium salt, magnesium salt and the like. As the cooling agent, menthol, camphor, peppermint oil, eucalyptus oil, peppermint oil, chlorobutanol and menthyl lactate are preferable, and menthol is particularly preferable.

The pharmaceutical composition of the present invention comprises a hyperlipidemic agent, a mucosal protective agent, a parasympathetic nerve blocker, a digestive enzyme, a vitamin drug, a bactericidal disinfectant, and an astringent, in addition to the above-mentioned components. Ingredients such as local anesthetics and herbal medicines can be appropriately blended alone or mixed with each other.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The pharmaceutical composition of the present invention can usually be administered to an adult by oral administration in divided doses of 1 to several times a day. This dose depends on age, weight,
It can be increased or decreased depending on the person to be used, such as a medical condition.

The carrier used for the preparation of the preparation includes excipients such as lactose, starch, sugar, mannitol and crystalline cellulose, binders such as hydroxypropylcellulose, hydroxymethylcellulose, gelatin and PVP, carboxymethylcellulose and low Degree of substitution There are disintegrants such as hydroxypropyl cellulose, lubricants such as magnesium stearate, hydrogenated castor oil, and talc. In addition to these, solubilizers, buffers, preservatives, fragrances, dyes, etc. are used as necessary. be able to.

The pharmaceutical composition of the present invention is provided as an oral dosage form such as tablets, capsules, caplets, granules, chewable agents and jellies prepared by a conventional method. And tablets and granules are suitable. Regarding the production of the preparation, it can be produced according to each item of the general rules for preparation of Japanese Pharmacopoeia. Colestimide in the present invention,
The amount of colestimide per day for an adult is 1.5 to 4 g. This is 70 to 94% by weight as a concentration in the preparation. Polycarbophil and its salts are 1.5 to 3 g of polycarbophil calcium per adult per day. This is 88 to 95% by weight as a concentration in the preparation. In addition, menthol, camphor, peppermint oil, eucalyptus oil, peppermint oil, chlorobutanol, and menthyl lactate, which are refreshing agents, each have a concentration of 0.001 to 1.0% by weight, preferably 0.0.
It is from 0.5 to 0.5% by weight.

[0012]

EXAMPLES The present invention will be described in more detail with reference to examples and test examples, but the invention is not limited to the following examples. (Example 1) Cholestimide was pulverized with a pin mill (Hosokawa Micron Co., Ltd., 10,000 revolutions) to obtain 1000.
g was weighed, and a fluidized bed granulator (manufactured by Freund, FLO-
Hydroxypropylcellulose (HPC-L, Shin-Etsu Chemical Co., Ltd.), which was placed in 1) and separately dissolved in purified water to 10%
Was sprayed and granulated and dried continuously. The obtained granules are sieved with 24 mesh and crospovidone is added to 6.
5 g was added and mixed well in a plastic bag, and then magnesium stearate (of plant origin) was added and further mixed to obtain granules for tableting. The obtained granules for tableting were made into caplets of 530 mg per tablet using a tableting machine (Kikusui company, Correct 18K). Put the obtained 1800 tablets of caplets in a doria coater (DRC300, manufactured by Paulec),
5 mg of menthol-containing film liquid (as solid content)
The coated tablets were coated to give 535 mg of coated tablets.

Colestimide 1000 g Hydroxypropyl cellulose 50 g Crospovidone 6.5 g Magnesium stearate 3 g (Film solution) dl-menthol 14.6 g Sugar ester S1670 7.33 g Glycerin 7.33 g Pullulan 73.3 g Purified water 997 g (Example 2) Cholestimide was crushed with a pin mill (Hosokawa Micron Co., Ltd., 10,000 revolutions) to obtain 1000.
g, weigh 160 g corn starch, 100 g lactose,
50 g of hydroxypropyl cellulose (HPC-L-fine powder) was added and mixed, and the yard grinder (screen diameter: 1
mm), add an appropriate amount of purified water / ethanol mixture (6: 4), knead, and extrude granulator (screen diameter:
0.7 mm) to produce cylindrical granules and continuously dried. 1000 g of the obtained granules were weighed and put into a fluidized bed coating machine with a draft tube (GPCG1 type, manufactured by Glatt), coated with 5% (as solid content) of a film solution containing mint oil, and magnesium aluminometasilicate. A small amount (0.1%) of a powder obtained by mixing (1: 1) with and apple flavor was added to produce 1.05 g of a granule. Colestimide 1000 g Corn starch 160 g Lactose 100 g Hydroxypropyl cellulose 50 g (Film solution) Mint oil 20 g Sugar ester S1670 7.33 g Glycerin 7.33 g Pullulan 73.3 g Purified water 997 g (Example 3) Polycarbophil calcium 750 g, polyvinyl polypyrrolidone 42 g After weighing and mixing, the mixture was pulverized by a yarn crusher (screen diameter: 0.7 mm), granulated by a stirring granulator (vertical granulator 5L, manufactured by Powrex) and continuously dried. 635 of them
g was weighed, crospovidone (24 g) and magnesium stearate (2.4 g) were added and mixed well to prepare tableting granules. One tablet granule is set to 275 mg and the diameter is 8.5 m.
Tableting using m punch and mortar (collect 12K, Kikusui)
did. The obtained tablets were put in a doria coater (DRC300, manufactured by Paulec), coated with 5 mg (as solid content) of a film solution containing eucalyptus oil, and 28 tablets each.
0 mg coated tablet was obtained.

[0014] Polycarbophil calcium 601g Polyvinyl polypyrrolidone 33.7 g Crospovidone 24g Magnesium stearate 2.4g (Film liquid) Eucalyptus oil 20g Sugar Ester S1670 7.33g Glycerin 7.33g Pullulan 73.3g Purified water 997g

(Test Example) Study on Improving Ingestion Feeling The composition of Example 1 and Comparative Examples 1 to dl
-Composition lacking menthol was prepared to give 3 doses each. Sense of use 10 adults (5 men, 5 women) took the above-mentioned drug together with a glass of water (200 ml), and a questionnaire on the feeling of use was conducted for each composition. It should be noted that each dosage feeling was tested at intervals of at least 10 minutes.

[0016] The questionnaire is 4: easy to take, no problem in taking, 3: no difficulty in taking, although no difficulty in taking,
Evaluations were made by adding 2: difficult to take and difficult to take, 1: unpleasant to take and unacceptable, and a total evaluation score of all panelists was obtained.
The results are shown in Table 1. As a result, the composition containing dl-menthol had a high score and the feeling of ingestion was improved.

[0017]

[Table 1]

[0018]

[Effects of the Invention] As a constituent component, it is selected from the group consisting of cholestimide, polycarbophil and salts thereof which are resin preparations, and menthol, camphor, peppermint oil, eucalyptus oil, peppermint oil, chlorobutanol and menthyl lactate which are cooling agents. A pharmaceutical composition which inhibits or significantly reduces and removes unpleasant sensations such as dysphagia caused by taking colestimide, polycarbophil, and salts thereof by blending any one or two or more of the above. Was obtained.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 47/46 A61K 47/46 (72) Inventor Keishi Ichihara 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceuticals Co., Ltd. (72) Inventor Joji Nakagami 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Inventor Ichiro Okuhira 3-24-1 Takada, Toshima-ku, Tokyo Taisho In-house F-term (Reference) 4C076 DD37 DD40 DD45 EE53 FF52 4C084 AA27 MA05 MA52 NA09 ZA66 ZC33 4C086 AA01 FA02 FA07 MA02 MA05 MA52 NA09 ZA66 ZC33

Claims (3)

[Claims] 1. A pharmaceutical composition comprising a resin formulation and a cooling agent. 2. The pharmaceutical composition according to claim 1, wherein the resin preparation is one selected from the group consisting of colestimide, polycarbophil and salts thereof. 3. The pharmaceutical composition according to claim 1, wherein the cooling agent is one or more selected from the group consisting of menthol, camphor, peppermint oil, eucalyptus oil, peppermint oil, chlorobutanol and menthyl lactate.